This invention relates to novel antiviral peptides and, more particularly, to small peptides which interfere with the final stages of virus intracellular replication.
Although powerful chemotherapeutic agents have been developed for successful treatment of bacterial infections, e.g. the penicillins and cephalosporins, no such comparable antiviral therapies have been devised. Despite the vast number of compounds screened in the past several decades and the multi-millions of dollars spent on development, only a handful of drugs have had limited clinical utility in controlling viral infections. Among the types of compounds having been found to have limited success, the following are illustrative:
Aminoquinolines, e.g. chloroquin (U.S. Pat. No. 2,233,970); PA1 Amantadine (U.S. Pat. No. 3,310,469); PA1 Phosphonoacetic acid or PAA (U.S. Pat. No. 3,767,795); PA1 Phosphonoformic acid (U.S. Pat. 4,771,041); PA1 Purine and pyrimidine nucleosides, e.g. 9-.beta.-D-arabinofuranosyladenine (vidarabine or ara-A, U.S. Pat. No. 3,616,208); PA1 AraH.sub.x MP (U.S. Pat. No. 4,093,714); PA1 2'-Deoxy-5-iodouridine (idoxuridine or IDU) and derivatives (U.S. Pat. No. 4,000,260); PA1 Ribavirin (U.S. Pat. No. 3,798,209); PA1 Acyclovir and derivatives (U.S. Pat. No. 4,199,574); PA1 3'-Azido-3'-deoxythymidine (azidothymidine or AZT) (U.S. Pat. No. 4,724,233).
A significant problem that exists with the analogs of pyrimidines and purines is that they are most often as toxic to an uninfected cell as to virus multiplication in that cell.
Any attempt to treat a viral infection must take into account the various methods by which the virus interacts with the host cell. Viruses consist of a shell of protein enclosing a core of nucleic acid, either ribonucleic acid (RNA) or deoxyribonucleic acid (DNA), that codes for viral reproduction. That is, the RNA or DNA is the genetic material which carries the genes specifying the enzymes and structural proteins that the virus needs to interact with the host cell and reproduce itself. This protein shell also serves as a protective coat to keep the nucleic acid intact and prevent enzymic destruction. Some viruses also contain, in addition to their protein coat, an outer covering referred to as an envelope. This envelope consists of a lipid bilayer which is derived from membranes of the cell in which the virus has replicated and glycoproteins whose sequences are encoded in the virus genome. The structure of these glycoproteins consists of an outer, extra-cellular domain, a transmembranal domain and a cytoplasmic domain which is localized to the interior of the lipid bilayer. Current antiviral therapy thus has attempted to exploit the subtle molecular contrasts between virus and host and to develop antiviral compounds that will interfere with biochemically defined virus-specific functions. See, for example, Cohen, Science 205, 964-971 (1979); Dolin, Science 227, 1296-1303 (1985); Robins, Chem. & Eng. News 64, 28-40 (1986); Hirsch and Kaplan, Scientific Amer. 256(4), 76-85 (1987); and Varmus, Science 240, 1427-1435 (1988).